CA - Arvinas: Positive Breast Cancer Data Leads To Other Developments

2023-12-15 16:20:04 ET

Summary

• Positive interim data achieved by Arvinas, Inc. from phase 1b study using vepdegestrant for the treatment of patients with ER+/HER2- advanced or metastatic breast cancer patients respectively.
• Two ongoing phase 3 studies being advanced are using vepdegestrant alone or in combination to treat 2nd-line and 3rd-line ER+/HER2- advanced or metastatic breast cancer patients respectively.
• The global metastatic breast cancer market is expected to reach $41.74 billion by 2030; more than 2 out of every 3 breast cancers are both hormone receptor-positive and HER2-negative.
• Additional phase 3 studies could be initiated, using vepdegestrant with other CDK4/6 inhibitors for the treatment of ER+/HER2- advanced or metastatic breast cancer patients, pending positive regulatory discussion outcomes.

Arvinas, Inc. ( ARVN ) has made great progress in being able to advance its pipeline, that's because it, along with its partner Pfizer Inc. ( PFE ), was able to report positive results from an ongoing phase 1b study which used vepdegestrant [ARV-471] in combination with IBRANCE for the treatment of patients with locally advanced or metastatic Estrogen receptor positive /Human epidermal growth factor 2 [HER2] negative [ER+/HER2-] breast cancer. Such positive data bodes well for an ongoing phase 3 program, because interim data from this phase 1b study showed that the combination was effective in helping these patients in terms of efficacy and to also be able to stay on a tolerable type of treatment.

Despite the current standard of care for advanced breast cancer, many patients progress regardless. Such a combination could offer hope for these patients. There are two ongoing phase 3 studies known as VERITAC-2 and VERITAC-3, which are using this drug alone or in combination to treat breast cancer patients in the 2nd-line and 1st-line settings, respectively. Should regulatory authorization be given, there is potential for Arvinas and its partner Pfizer to be able to include new cohort combinations as part of this breast cancer program. That would be to include the use of cyclin-dependent kinase [CDK] inhibitors in both the 1st-line and 2nd-line treatment setting for these patients.

Positive Interim Results From Phase 1B Study Means Two Advancements

As I stated above, there were positive interim results released from the phase 1b study, which used vepdegestrant [AR-471] in combination with Pfizer's IBRANCE for the treatment of patients with locally advanced or metastatic ER positive/human epidermal growth factor negative [ER+/HER2-] breast cancer. Such positive data was presented at the 2023 San Antonio Breast Cancer Symposium [SABCS]. Out of the 31 advanced breast cancer patients evaluable from this phase 1b study, 13 of them had responded to this combination therapy. Thus, there was a 42% Objective Response Rate [ORR] established . Along with the fact that as of an 11-month median follow-up, there was a median progression-free survival [mPFS] of 11.1 months obtained.

These results are pretty good, especially when you put it into context that these women took an average of at least 4 prior lines of therapy before being given this vepdegestrant combination. The global metastatic breast cancer market is expected to reach $41.74 billion by 2030 . This is the total market opportunity, which is a large one, but there is something very important to consider as it relates to this indication. Arvinas is only targeting advanced or metastatic breast cancer patients who are Estrogen Receptor positive or Human epidermal growth factor receptor 2 negative.

This is still going to be a large market opportunity. Why is that? It is because more than 2 out of every 3 breast cancers are both hormone receptor-positive and HER2-negative. This positive interim data leads to two advancements as it relates to this specific program, which is the possible positive data to be released from the two ongoing phase 3 studies and expansion cohorts incorporating a CDK4/6 inhibitor with vepdegestrant and IBRANCE [palbociclib].

In terms of the phase 3 program, there are two ongoing studies known as VERITAC-2 and VERITAC-3. The late-stage VERITAC-2 study uses vepdegestrant as a monotherapy for the treatment of patients with 2nd-line ER+/HER2- advanced or metastatic breast cancer. On the other hand, the late-stage VERITAC-3 study uses vepdegestrant in combination with IBRANCE for the treatment of 1st-line ER+/HER2- advanced or metastatic breast cancer patients. The positive interim data released at the SABCS 2023 medical meeting bodes well for both of these phase 3 studies. However, even if efficacy doesn't end up great, there might be another shot on goal for this program. Both Arvinas and its partner Pfizer want to get authorization from regulatory authorities to expand this development program. That is, to incorporate new studies which are going to be evaluating vepdegestrant and IBRANCE together with other CDK4/6 inhibitors. It is the plan to initiate new phase 3 studies, which are going to be additional combinations to treat these advanced or metastatic ER+/HER2- breast cancer patients as follows:

• Phase 3 trial, using vepdegestrant + IBRANCE and other CDK4/6 inhibitors for treatment of 2nd-line ER+/HER2- advanced or metastatic breast cancer patients.
• Phase 3 trial, using vepdegestrant + Pfizer's novel CDK4/6 inhibitor [PF-07220060] for the treatment of 1st-line ER+/HER2- advanced or metastatic breast cancer patients.

One thing to note is that CDK4/6 proteins are found in both healthy cells and cancerous cells. The problem is that this protein is responsible for causing cancerous cells to grow and divide uncontrollably. Thus, it is thought that by inhibiting this protein it could slow or halt the progression of cancer cells from growing. This, in turn, could ultimately provide superior outcomes for these breast cancer patients.

Financials

According to the 10-Q SEC Filing , Arvinas had cash, cash equivalents, restricted cash and marketable securities of $1.04 billion as of September 30th 2023. A part of the reason for the cash on hand during the quarter was because it sold 1,449,275 shares of its common stock in an "at-the-market offering" for aggregate gross proceeds of $37.1 million. It believed that it would have enough cash on hand to fund its operations into 2026. However, despite having this expected cash runway, it chose to enter into a private placement agreement with a select group of institutional accredited investors. Based on such a private placement agreement made, it was able to earn up to an aggregate of $350 million before deducting expenses.

Risks To Business

There are several risks that investors should be aware of before investing in Arvinas. The first risk to consider would be with respect to the ongoing phase 3 program, which is using vepdegestrant both alone as a monotherapy and in combination with IBRANCE for the treatment of 1st-line and 2nd-line advanced or metastatic ER+/HER2- breast cancer patients respectively. Even though this company was able to achieve positive interim data from the phase 1b study using this combination in patients given an average of 4 prior therapies, there is no assurance that this will translate into positive data for one or both of the ongoing phase 3 studies.

A second risk to consider would be with respect to the expansion of the vepdegestrant program towards other new phase 3 studies. There is a plan for Pfizer and its partner Arvinas to get authorization from regulators to begin new studies incorporating other CDK4/6 inhibitors. There is no assurance that they will be able to receive authorization from regulators to begin new late-stage studies, nor that positive data will eventually be released from them.

A third and final risk to consider would be with respect to the financials of this company. Despite having enough cash runway until 2026, it chose to enact a cash raise. From looking at the SEC Filings, there is a history pattern of one big cash raise through the sale of common stock and then one ATM issuance per year. If such a pattern is followed, then it is possible that it could enact another cash raise in 2024 at some point, along with additional funds being raised through an ATM.

Conclusion

Arvinas, Inc. has done well to advance its pipeline, especially since it has been able to advance the use of its drug vepdegestrant for the treatment of patients with 1st-line/2nd-line ER+/HER2- advanced or metastatic breast cancer patients. It had reported positive interim results from its ongoing phase 1b study using the combination of vepdegestrant + IBRANCE for these patients who had already gone through and failed an average of at least 4 prior therapies. The hope is that the company will be able to either advance vepdegestrant alone or in combination for the 2nd-line or 1st-line setting treatments respectively. However, even if it doesn't ultimately succeed with these trials, it is already in the process of initiating new ones. These new ones are going to use vepdegestrant with other CDK4/6 inhibitors, including possibly Pfizer's one known as PF-07220060.

Vepdegestrant is only one aspect of the pipeline. There is another drug known as ARV-766 which is a protein degrader which targets the androgen receptor [AR], which is being developed for the treatment of patients with metastatic castration-resistant prostate cancer [mCRPC]. The global metastatic castrate-resistant prostate cancer treatment market size could reach $17.71 billion by 2029 . This drug has a completely different profile over another protein-degrader for mCRPC known as bavdegalutamide. Phase 2 dose expansion progression-free survival [PFS] data, using ARV-766 for the treatment of this patient population, is expected to be released in 2024. Another possible catalyst for investors to look forward to would be a phase 3 trial initiation using ARV-766 to treat patients with mCRPC. Regulatory discussions for such a late-stage study are expected in Q2 of 2024 and then a late-stage trial could be initiated thereafter.

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